Food allergy

Food allergies are IgE, non-IgE, or mixed hypersensitivity reactions to food allergens. They are the most common cause of anaphylaxis. Young children are commonly affected, with onset usually in the first two years of life. IgE-mediated reactions are the most common type of food allergy and have an onset within minutes after ingestion, while mixed or non-IgE reactions are usually delayed and limited to the gastrointestinal tract. Clinical features include urticaria, angioedema, wheezing, rhinorrhea, and abdominal pain. Differential diagnoses include food intolerance and reactions to non-food allergens. A thorough patient history must be obtained to identify a potential allergen, with allergist consultation for testing (e.g., skin prick test, allergen-specific IgE test). Additional interventions (e.g., oral food challenge) may be required for inconclusive results or suspected mixed or non-IgE reactions. Avoidance of triggers is the mainstay of management. Other therapies (e.g., oral immunotherapy, omalizumab) may be considered in select patients. The primary prevention method is the early introduction of potentially allergenic foods.

• Most common cause of anaphylaxis-related emergency admissions
• Prevalence (international): 2–5% of adults, 8% of children ^[1][2]

Risk factors for food allergies ^[3][4]

• Most significant risk factor: severe atopic dermatitis
• Others: other forms of atopy (e.g., mild to moderate atopic dermatitis, an existing food allergy) or a parent with atopy ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Hypersensitivity reaction; (IgE, non-IgE, or mixed) against select ingredients in food
• The most common food allergens (the big nine food allergens) in the US are: ^[5][6]
  • Legumes: peanuts (most common allergen), soybeans
  • Tree nuts
  • Animal products: cow's milk, chicken eggs, fish, shellfish
  • Other: wheat, sesame

• Commonly IgE-mediated: type I hypersensitivity reaction (immediate onset; within minutes to 2 hours of ingestion)
• Mixed IgE/non-IgE-mediated and non-IgE-mediated reactions are also possible (delayed onset; hours to days after ingestion).

Clinical features of food allergy vary from mild symptoms (e.g., isolated skin involvement) to life-threatening anaphylaxis. ^[2]

• Skin (most common)
  • Pruritus, erythema
  • Urticaria, angioedema
• Respiratory
  • Sneezing, nasal pruritus, rhinorrhea
  • Laryngeal edema
  • Wheezing, dyspnea
• Gastrointestinal
  • Symptoms of oral allergy syndrome
  • Nausea, vomiting
  • Abdominal pain
  • Diarrhea, blood or mucus in stool
• Cardiovascular
  • Hypotension
  • Tachycardia, dysrhythmias
• CNS: headache
• Features of associated conditions, e.g.:
  • Asthma
  • Atopic dermatitis
  • Allergic rhinitis
  • Eosinophilic esophagitis

Non-IgE or mixed reactions typically have delayed onset (hours to days) and are limited to the skin and GI tract. ^[2][7]

Respiratory and cardiovascular manifestations can be fatal.

Food protein-induced allergic proctocolitis of infancy (FPIAP)

• Definition: a type of delayed inflammatory non-IgE-mediated food allergy typically seen in young infants that affects the distal colon
• Epidemiology: primarily affects young infants (typically manifests at 2–8 weeks of age)
• Etiology
  • Hypersensitivity reaction to certain foods, most commonly cow's milk, followed by soy protein, rice, and eggs ^[8]
  • Associated with a personal and family history of atopy ^[9]
• Clinical features
  • Insidious progression of symptoms over several months
    • Rectal bleeding
    • Increased stool frequency
    • Streaks of mucus in the stool
    • Abdominal pain
  • Affected infants typically appear otherwise healthy.
• Diagnostics: mainly a clinical diagnosis based on patient history and clinical features
  • Patient history: evaluation of infant's and mother's diet
  • Laboratory testing: may reveal eosinophilia, mild iron deficiency anemia, and/or increased fecal calprotectin
• Differential diagnosis
  • Necrotizing enterocolitis
  • Gastrointestinal infection (e.g., with Campylobacter)
  • Anal fissure
  • Intussusception
  • Meckel diverticulum
• Management
  • Removal of offending foods from the infant's diet
    • Breastfed infants
      • Elimination of all dairy and soy products from the mother's diet
      • Continue breastfeeding
    • Formula-fed infants: switching to a hydrolyzed formula (e.g., hydrolyzed casein)
  • The offending foods should be carefully reintroduced to assess tolerance after one year of age.
• Complications: chronic colitis and/or persistent food allergy (rare)
• Prognosis
  • Gross rectal bleeding usually improves within 3–4 days of removing the offending food. ^[9]
  • FPIAP usually resolves spontaneously by one year of age. ^[10]

Pollen-associated food allergy syndrome ^[6][7][11]

• Definition: an IgE-mediated reaction to the ingestion of certain raw fruits, vegetables, and nuts in individuals with pollen allergy
• Etiology: cross-reactivity between pollen allergens and proteins in certain foods
  • Melons, kiwis, bananas, and cucumbers in individuals allergic to ragweed pollen
  • Apples, peaches, and hazelnuts in individuals allergic to birch pollen
• Clinical features
  • Pruritus, tingling, and/or edema of the lips, tongue, palate, and pharynx
  • Onset within minutes of ingesting foods
  • Symptoms are typically mild and temporary, but anaphylaxis may occur.
• Diagnostics: See “Diagnosis.”
• Treatment: See “Treatment.”

Approach ^[2][6][12]

• Clinical evaluation to identify the potential allergen and exclude differential diagnoses should include:
  • Type of ingested foods and preparation (e.g., raw vs. cooked)
  • Amount of ingestion and timing relative to symptoms
  • Type of reaction (e.g., limited to skin, respiratory symptoms) and context (e.g., stress, mother's diet in breastfed infants)
  • Risk factors for food allergy, e.g., severe atopic dermatitis, eosinophilic esophagitis ^[7]
• Consider referral to an allergist for diagnostic testing.

For patients appearing unwell, use the ABCDE approach and rule out serious conditions (e.g., intussusception).

Diagnosis of food allergy is primarily clinical. Laboratory studies and other tests may support the diagnosis.

Diagnostic studies ^[2][6][12]

An allergist may perform the following studies in patients with a strong clinical suspicion of IgE-mediated food allergy.

• Skin prick test (SPT): first-line test for suspected IgE-mediated food allergy
• Allergen-specific IgE test (sIgE)
  • Indications
    • Inconclusive or contraindicated SPT (e.g., high risk of anaphylaxis, uncontrolled asthma, taking medications for chronic conditions)
    • Suspicion of a specific allergy, e.g., alpha-gal syndrome
  • Methods
    • ELISA: preferred
    • Radioallergosorbent test : no longer used

Total serum IgE is not useful for diagnosis because low or normal levels do not exclude an IgE-mediated reaction. ^[12]

A positive SPT or sIgE indicates sensitization to an allergen but does not confirm a food allergy. Always correlate with the patient's clinical evaluation. ^[6][7]

Additional evaluations ^[2][7]

• Double-blind oral food challenge
  • Indications: gold standard test for food allergy ^[2][7]
  • Method: Under medical surveillance, the patient is given different potential food allergens in increasing doses.
  • Diagnosis is confirmed if symptoms occur (e.g., tingling, pruritus, urticaria, angioedema).
• Elimination diets
  • Indications
    • Inconclusive laboratory studies
    • Suspected mixed or non-IgE mediated food allergy (e.g, FPIAP, eosinophilic esophagitis)
  • Method: The suspected allergen is eliminated from the patient's diet.
  • Diagnosis is confirmed if symptoms resolve without the need for antihistamines or other medications for food allergy.
• Other methods (may be performed if initial studies are negative): intradermal tests, basophil activation tests ^[6]

Broad elimination diets (i.e., restricting multiple foods) are associated with significant malnutrition. ^[7]

• Reaction to non-food allergens (e.g., medications, Hymenoptera stings)
• Anorexia nervosa
• Chronic urticaria
• Food intolerance, e.g., lactose intolerance, fructose intolerance
• Celiac disease
• Infantile colic
• GERD, IBD
• Neurologic responses to temperature or capsaicin (e.g., rhinitis from hot or spicy foods)

The differential diagnoses listed here are not exhaustive.

There is no specific treatment for food allergy. Management is primarily supportive. ^[6][7]

• Anaphylaxis management: if diagnostic criteria for anaphylaxis are met
  • Administer IM epinephrine.
  • Initiate immediate hemodynamic support (e.g., IV fluids, supplemental oxygen).
  • Alert the ICU and/or consult anesthesiology.
  • See “Management of anaphylaxis” and “Management of angioedema” for treatment algorithms.
• Avoidance of identified allergens ^[6][7]
  • First-line management
  • Educate patients on food cross-contamination (e.g., contact with allergens during food preparation).
• Symptomatic management: second-generation antihistamines (e.g., cetirizine ) for mild symptoms
• Oral immunotherapy: ingestion of increasing doses of a specific food allergen in a controlled setting to reduce the risk of anaphylaxis caused by accidental exposures
  • Effective in patients with allergy to peanuts, milk, and eggs
  • Anaphylaxis may occur during oral immunotherapy.
  • Palforzia (peanut allergen powder) is the only oral immunotherapy product approved by the FDA. ^[13]
• Omalizumab: considered in select patients (based on serum IgE and body weight) ^[14]

Peanuts and tree nuts are the most common causes of lethal allergic reactions, including anaphylaxis. Educate patients with these allergies on the use of an epinephrine autoinjector. ^[2][6]

• Most children with milk, egg, soy, and/or wheat allergies outgrow them by 5 years of age. ^[2][6]
• Children with food allergies are at increased risk of developing asthma and allergic rhinitis. ^[2]
• Adult-onset food allergies usually remain for life.

The early introduction of potentially allergenic foods can prevent the development of food allergies. ^[3][4]

• Recommendations ^[3]
  • Introduce products containing peanuts and cooked eggs around 6 months of age. ^[3][4]
  • Encourage the introduction of other potentially allergenic foods between 6 months and 1 year of age. ^[3]
  • Ensure infants and children have diverse diets and regularly consume potentially allergenic foods.
• Screening
  • Not required, even in individuals with food allergy risk factors
  • Concerns about introducing allergenic foods at home: Refer for skin prick testing or obtain a specific IgE level. ^[3][15]
  • Positive skin prick testing or specific IgE: Offer an expedited supervised oral food challenge.

To avoid choking, introduce potentially allergenic foods in age-appropriate forms (e.g., diluted or thinned peanut butter, items containing peanut powder, and peanut puffs). ^[3]

Dietary restrictions during pregnancy and lactation, exclusive breast milk, and the use of hydrolyzed formula do not prevent food allergies in children. ^[3]